Embolia colesterínica en miembro superior izquierdo asociado a fístula arteriovenosa / Cholesterol embolism in the left upper limb associated with venous artery fistula

RESUMEN El embolismo por cristales de colesterol (ECC) es una complicación de la enfermedad arterioesclerótica en la que el desprendimiento de fragmentos de placa de ateroma, principalmente de grandes arterias, provoca oclusión de pequeños vasos. Esta entidad, también llamada ateroembolia o síndrome de los dedos del pie azules, es más frecuente en pacientes de edad avanzada y después de procedimientos invasivos intravasculares. Se manifiesta con cianosis, livedo reticularis, necrosis y úlceras asociado a manifestaciones renales y gastrointestinales. Se presenta un paciente trasplantado renal y portador de fístula arteriovenosa trombosada izquierda con ateroembolia localizada en mano homolateral.

ABSTRACT The cholesterol crystal embolism (ECC) is a complication of arteriosclerotic disease in which the detachment of fragments of atheromatous plaque mainly from large arteries, causes occlusion of small vessels. This entity, also called atheroembolism or blue toe syndrome, is more common in elderly patients and after intravascular invasive procedures. It manifests with cyanosis, livedo reticularis, necrosis and ulcers associated with renal and gastrointestinal manifestations. We present a renal transplant patient with a left thrombosed arteriovenous fistula with atheroembolism located in homolateral hand.

Low-density lipoprotein apheresis ameliorates monthly estimated glomerular filtration rate declines in patients with renal cholesterol crystal embolism.

The incidence of cholesterol crystal embolism (CCE) has increased along with increases in the prevalence of atheromatous diseases and intravascular procedures. CCE frequently results in the deterioration of renal function, which sometimes leads to end-stage renal failure. Although there has been no established therapy for CCE, the possibility that low-density lipoprotein apheresis (LDL-A) is an effective therapy for renal CCE was previously reported. However, whether LDL-A improves renal CCE remains uncertain. This study aimed to evaluate the effectiveness of LDL-A in renal CCE patients. Twelve renal CCE patients (9 men and 3 women, mean age 70.6 ± 1.7 years) were included in this retrospective study. All patients had received LDL-A therapy, and estimated glomerular filtration rate (eGFR) values were examined before and after LDL-A. In addition, monthly changes in eGFR before and after LDL-A were calculated for each patient. At initial diagnosis of renal CCE, the eGFR was 35.2 ± 4.8 mL/min/1.73 m(2). At the initiation of LDL-A, the eGFR significantly decreased to 11.0 ± 1.2 mL/min/1.73 m(2), and monthly changes in eGFR reached -7.2 ± 2.5 mL/min/1.73 m(2)/month. After the initiation of LDL-A, the progression of renal dysfunction stabilized in nearly two-thirds of patients, and monthly changes in eGFR after LDL-A significantly diminished to -0.3 ± 0.7 mL/min/1.73 m(2)/month (p < 0.05 vs. before LDL-A). Although 4 patients had to undergo hemodialysis, all patients were alive over 1 year after the initiation of LDL-A. LDL-A therapy ameliorated renal dysfunction in renal CCE patients.

ST-elevation myocardial infarction as a complication of retrograde chronic total occlusion recanalization.

With the advent of new tools and techniques including the retrograde approach, success rates for recanalization of chronic total occlusion (CTO) have improved. Numerous cardiac and extracardiac complications during retrograde CTO recanalization have been described. To date the development of ST-segment elevation myocardial infarction (STEMI) with retrograde recanalization as a result of atheroembolization has not been reported. We report such a case following retrograde recanalization of a totally occluded right coronary artery.

Cholesterol crystal embolization (CCE): Improvement of renal function with high-dose corticosteroid treatment.

Cholesterol crystal embolization (CCE) is an important and often under-diagnosed cause of renal insufficiency in patients with atherosclerosis. So far, only statins are the mainstay of therapy and the role of corticosteroids is controversial. We describe a 57-year-old gentleman who presented with accelerated hypertension and renal failure three months after coronary angiogram. Renal biopsy showed cholesterol clefts in the arteriole. Initially, management with anti-hypertensives alone (already receiving statins since angiogram) was unsuccessful. A trial of high-dose corticosteroids resulted in an improvement of the general condition in the next two days, and the serum creatinine reduced gradually to 1.6 mg/dL over the next one month. In conclusion, high-dose corticosteroids are useful in the treatment of CCE associated renal failure, especially in cases with no spontaneous recovery of function.

The seabed-like appearance of atherosclerotic plaques: three-dimensional transesophageal echocardiographic images of the aortic arch causing cholesterol crystal emboli.

Cholesterol crystal embolism (CCE) is a rare but important complication of endovascular procedures or anticoagulation therapy. An 84-year-old man was referred to the Gunma University Graduate School of Medicine with the diagnosis of acute myocardial infarction. After successful emergency coronary angioplasty, his serum creatinine level increased continuously. A subsequent skin biopsy confirmed that the patient had CCE. Transesophageal echocardiography (TEE) clearly demonstrated the mobile mass protruding from the complex atheroma. Three-dimensional TEE provides more precise and attractive volumetric images of the atherosclerotic plaque than two-dimensional TEE. In addition, the findings of this case revealed contrast media-induced nephropathy and CCE as possible causes of renal dysfunction after endovascular procedures.

Atheroembolic renal disease.

Atheroembolic renal disease develops when atheromatous aortic plaques rupture, releasing cholesterol crystals into the small renal arteries. Embolisation often affects other organs, such as the skin, gastrointestinal system, and brain. Although the disease can develop spontaneously, it usually develops after vascular surgery, catheterisation, or anticoagulation. The systemic nature of atheroembolism makes diagnosis difficult. The classic triad of a precipitating event, acute or subacute renal failure, and skin lesions, are strongly suggestive of the disorder. Eosinophilia further supports the diagnosis, usually confirmed by biopsy of an affected organ or by the fundoscopic finding of cholesterol crystals in the retinal circulation. Renal and patient prognosis are poor. Treatment is mostly preventive, based on avoidance of further precipitating factors, and symptomatic, aimed to the optimum treatment of hypertension and cardiac and renal failure. Statins, which stabilise atherosclerotic plaques, should be offered to all patients. Steroids might have a role in acute or subacute progressive forms with systemic inflammation.

Lack of association between dialysis modality and outcomes in atheroembolic renal disease.

BACKGROUND AND OBJECTIVES: Atheroembolic renal disease (AERD) can require dialytic support. Because anticoagulation may trigger atheroembolization, peritoneal dialysis may be preferred to hemodialysis. However, the effect of dialysis modality on renal and patient outcomes in AERD is unknown. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS: A subcohort of 111 subjects who developed acute/subacute renal failure requiring dialysis was identified from a larger longitudinal study of AERD. The main exposure of interest was dialysis modality (peritoneal versus extracorporeal therapies). Logistic regression was used to study the probability of renal function recovery. Times from dialysis initiation to death were studied using Cox's regression. RESULTS: Eighty-six patients received hemodialysis and 25 received peritoneal dialysis. The probability of renal function recovery was similar by dialysis modality (25% among hemodialysis patients and 24% among peritoneal dialysis patients; P = 0.873). During follow-up, 58 patients died, 14 among peritoneal patients and 44 among hemodialysis patients (P = 0.705). In multivariable analysis, gastrointestinal tract involvement and use of statins maintained an independent effect on the risk of patient death. CONCLUSIONS: This study does not support the notion that one dialysis modality is superior to the other. However, the observational nature of the data precludes any firm conclusions.

Angina crónica estable: fisiopatología y formas de manifestación clínica / Chronic stable angina: pathophysiology and clinical manifestations

La angina de pecho estable es la expresión clínica más común de la cardiopatía isquémica crónica sintomática y la manifestación inicial de la enfermedad coronaria en más de la mitad de los pacientes. La aterotrombosis es el proceso patológico implicado en su génesis y parece que la placa de ateroma estable es el principal sustrato anatómico que origina los síntomas. Se revisan las características histológicas de la placa estable, los diversos factores implicados en el desequilibrio entre el oxígeno aportado por la arteria coronaria y el demandado por el miocardio en riesgo y sus consecuencias en las células. Por último, se comentan las principales escalas de estratificación clínica de la angina crónica estable, sus implicaciones pronósticas y algunas peculiaridades de presentación en subgrupos de pacientes (AU)

Chronic stable angina pectoris is the most common clinical expression of symptomatic chronic ischemic heart disease and is the first manifestation of heart disease in more than half of patients. Atherothrombosis is the pathological process responsible for its development, and stable atheromatous plaque appears to be the principle anatomical substrate responsible for the associated symptoms. This article presents an overview of the histology of stable plaque, of the different factors involved in the imbalance between coronary artery oxygen supply and the oxygen demand of myocardial tissue at risk, and of the consequences of this imbalance at a cellular level. Finally, there is a discussion of the main measurement scales used for the clinical classification of chronic stable angina and their prognostic value, and of the particular forms of presentation in specific subgroup of patients (AU)

Oral antiplatelet therapy in the secondary prevention of atherothrombotic events.

Atherothrombosis is the leading cause of death worldwide and has a large economic impact. It is a pathologic process related to atherosclerosis, which leads to adverse clinical manifestations, including acute coronary syndrome, cerebrovascular disease, and peripheral arterial disease. Patients with atherothrombosis are at heightened risk for recurrent ischemic events or death, and therefore, secondary prevention is an important goal in the treatment of these patients. Antiplatelet therapies available for long-term secondary prevention include aspirin (acetylsalicylic acid), extended-release dipyridamole plus aspirin, and clopidogrel. A number of clinical trials have demonstrated the benefit of combined antiplatelet therapy in secondary prevention, supporting the recommendations made in current published guidelines. Although the efficacy and safety of antiplatelet agents is well established and supported by clinical trials, their utilization rate in patients with atherothrombosis remains suboptimal. Quality improvement initiatives have demonstrated effectiveness in promoting the awareness and implementation of treatment guidelines. This article reviews the benefits and risks of antiplatelet therapy in patients with cardiovascular disease with the aim of spurring greater adherence to treatment recommendations and, thereby, better patient outcomes.

Coronary no-reflow phenomenon: from the experimental laboratory to the cardiac catheterization laboratory.

Coronary no-reflow occurs commonly during acute percutaneous coronary intervention, particularly in patients with acute myocardial infarction and those with degenerated vein grafts. It is associated with a guarded prognosis, and thus needs to be recognized and treated promptly. The pathophysiology originates during the ischemic phase and is characterized by localized and diffuse capillary swelling and arteriolar endothelial dysfunction. In addition, leukocytes become activated and are attracted to the lumen of the capillaries, exhibit diapedesis and may contribute to cellular and intracellular edema and clogging of vessels. At the moment of perfusion, the sudden rush of leukocytes and distal atheroemboli further contributes to impaired tissue perfusion. Shortening the door-to-balloon time, use of glycoprotein IIb/IIIa platelet receptor inhibitors and distal protection devices are predicted to limit the development of no-reflow during percutaneous interventions. Distal intracoronary injection of verapamil, nicardipine, adenosine, and nitroprusside may improve coronary flow in the majority of patients. Hemodynamic support of the patient may be needed in some cases until coronary flow improves.

Enfermedad aterotrombótica coronaria: avances en el tratamiento antiplaquetario / Coronary atherothrombotic disease: progress in antiplatelet therapy

La plaqueta ha asumido un papel preponderante en la medicina cardiovascular gracias a la comprensión del síndrome coronario agudo (SCA) como un proceso aterotrombótico. Esto ha establecido el uso generalizado de agentes antiplaquetarios, como la aspirina, las tienopiridinas y los antagonistas de los receptores de la glucoproteína IIb/IIIa, en la prevención de las enfermedades isquémicas coronarias. Sin embargo, hay evidencias recientes de que no todos los pacientes reciben el tratamiento antiplaquetario adecuado, ya sea por el fenómeno de la «resistencia» o «respuesta variable» al fármaco o por un aumento en el riesgo de sangrado. Es más, la falta de eficacia de la combinación aspirina-clopidogrel en la prevención primaria ha cuestionado el concepto de «a mayor inhibición, mayor eficacia». Actualmente, los esfuerzos se centran en la mejora de los tratamientos antiplaquetarios en uso a fin de mejorar su efectividad y su seguridad. Se están desarrollando antagonistas alternativos de los receptores del ADP (prasugrel, AZD6140 y cangrelor) y de la trombina (E555 y SCH530348) que podrían ofrecer más inhibición de las plaquetas, más rápida y constante. Asimismo, el avance en el conocimiento de la estructura de la plaqueta y los mecanismos implicados en la formación del trombo puede dar lugar al descubrimiento de nuevas dianas terapéuticas. Este artículo revisa el papel fisiopatológico de las plaquetas en el proceso aterotrombótico, evalúa lo más actual del arsenal antiplaquetario actualmente en uso y comenta nuevas aproximaciones terapéuticas (AU)

Platelets are now regarded as playing a dominant role in cardiovascular medicine since our recent understanding of acute coronary syndrome as an atherothrombotic process. This development has led to the widespread use of antiplatelet agents, such as aspirin, thienopyridines and glycoprotein-IIb/IIIa receptor blockers, for the prevention of ischemic heart disease. Nevertheless, recent evidence suggests that not all patients receive appropriate antiplatelet therapy because there may be resistance or a variable response to the drug used or because of an increased risk of hemorrhage. Moreover, the reported lack of efficacy of the combination of clopidogrel and aspirin when used for primary prevention has raised concerns about the general concept that greater inhibition implies greater efficacy. At present, research efforts are focused on improving current antiplatelet treatment with the aim of increasing efficacy and safety. Alternative ADP-receptor antagonists (e.g., prasugrel, cangrelor and AZD6140) and thrombin-receptor antagonists (e.g., E5555 and SCH 530348) are being developed. They may provide faster, more potent and more stable platelet inhibition. In addition, new insights into platelet structure and into the mechanisms underlying thrombus formation could lead to the discovery of new therapeutic targets. This article reviews what is known about the pathophysiological role of platelets in the atherothrombotic process, considers the current state of the art in antiplatelet therapy, and provides a commentary on new therapeutic approaches (AU)

Cholesterol embolization syndrome induced by thrombolytic therapy.

Cholesterol embolization syndrome (CES) induced by thrombolytic therapy is a rare syndrome with a high incidence of morbidity and mortality. The variability in clinical presentations may cause a delay in diagnosis of CES. This article presents a comprehensive review of the English literature from January 1980 to December 2007 identifying all published case reports of CES induced by thrombolytic therapy. Multiple electronic databases were searched and relevant reference lists were hand searched to identify all case reports. Thirty cases of thrombolytic-induced CES were identified. Indications for thrombolysis were acute myocardial infarction (28 patients) and deep venous thrombosis (two patients). Skin and renal involvement were the most common presentations. Skin manifestations included livedo reticularis, rash, and skin mottling. Other clinical symptoms included cyanotic toes, gastrointestinal bleeding, or perforation, myalgias, retinal emboli, and CNS involvement. Morbidity and mortality were high. Outcomes included chronic hemodialysis in eight patients, four patients underwent amputations, seven patients developed or had progression of their chronic kidney disease, and seven deaths occurred.CES presents as multiorgan dysfunction and should be considered in the differential diagnosis of the symptom complex that may develop after thrombolytic therapy. Diagnosis of CES can be difficult as a result of the variable clinical presentations. A thorough clinical history and physical examination are essential first steps in establishing a diagnosis. Confirmatory diagnosis requires biopsy of the target organs. Measures to reduce the likelihood of recurrence should be taken and include avoidance of anticoagulation therapy and vascular procedures. Unfortunately, therapy remains supportive and the outcome is invariably poor.

Actualización del diagnóstico y tratamiento de la angina vasoespástica / Up-date of the diagnosis and treatment of vasospastic angina

La angina vasoespástica o variante de Printzmetal es una forma particular de cardiopatía isquémica, caracterizada por episodios espontáneos de dolor torácico acompañados de elevaciones transitorias del segmento ST durante dichos episodios, siendo estas alteraciones fundamentales para su diagnóstico, el cual se dificulta mucho en ausencia de las mismas, debiendo ser confirmado, si la sospecha clínica es elevada, mediante tests de provocación de vasoespasmo coronario, ya que de lo contrario puede haber casos infradiagnosticados o catalogados de otro tipo de patologías. La progresión de este tipo de angina hacia un infarto agudo de miocardio (IAM) por placa complicada es un hecho relativamente poco frecuente

Vasospastic or Prinzmetal's variant angina as it is also known is a special type of ischemic heart disease characterized by spontaneous episodes of chest pain accompanied by transitory ST segment elevations during the episodes. These alterations are essential for its diagnosis and it is difficult to diagnose it in their absence. If clinical suspicion is high, it should be confirmed by coronary vasospasm provocation tests, since, on the contrary, there may be cases that are not diagnosed or considered to be other types of diseases. Furthermore, progression of this type of angina to a myocardial infarction due to coronary stenosis is a relatively uncommon event (AU)

Metaloproteasas, remodelado vascular y síndromes aterotrombóticos / Metalloproteases, vascular remodeling and atherothrombotic syndromes

Las alteraciones en la síntesis y/o la degradación de la matriz extracelular (MEC) emergen como procesos clave en el desarrollo de la aterosclerosis y sus complicaciones trombóticas. Se ha observado una asociación entre los biomarcadores circulantes de la MEC y las manifestaciones clínicas y los factores de riesgo ateroscleróticos. Diversas metaloproteasas (MMP), endopeptidasas que degradan la MEC, como MMP-9 y 10, además de desempeñar un papel relevante en la fisiopatología del proceso aterotrombótico y contribuir a la expansión de los aneurismas arteriales, pueden ser de utilidad como biomarcadores de riesgo aterosclerótico y predictores de recurrencia de enfermedad coronaria y cerebrovascular. Aunque actualmente el papel de los inhibidores de MMP (TIMP) en el pronóstico cardiovascular es más incierto, la MEC puede representar una diana terapéutica atractiva en la aterotrombosis, y diversos inhibidores de las MMP se encuentran en fase de investigación clínica (AU)

Defects in the synthesis and breakdown of the extracellular matrix (ECM) are now seen as key processes in the development of atherosclerosis and its thrombotic complications. Correlations have been observed between circulating levels of ECM biomarkers and the clinical manifestations of and risk factors for atherosclerosis. Several matrix metalloproteinases (MMPs), endopeptidases that can degrade the ECM, such as MMP-9 and MMP-10, play important roles in the pathophysiology of atherothrombosis and contribute to the expansion of abdominal aortic aneurysms. Moreover, they may also be useful biomarkers of atherosclerotic risk and serve as predictors of coronary and cerebrovascular disease recurrence. Although at present the effect of tissue inhibitors of MMPs (TIMPs) on cardiovascular disease prognosis is still uncertain, the ECM could be a promising therapeutic target in atherothrombotic disease, and several MMP inhibitors are currently undergoing clinical trials Defects in the synthesis and breakdown of the extracellular matrix (ECM) are now seen as key processes in the development of atherosclerosis and its thrombotic complications. Correlations have been observed between circulating levels of ECM biomarkers and the clinical manifestations of and risk factors for atherosclerosis. Several matrix metalloproteinases (MMPs), endopeptidases that can degrade the ECM, such as MMP-9 and MMP-10, play important roles in the pathophysiology of atherothrombosis and contribute to the expansion of abdominal aortic aneurysms. Moreover, they may also be useful biomarkers of atherosclerotic risk and serve as predictors of coronary and cerebrovascular disease recurrence. Although at present the effect of tissue inhibitors of MMPs (TIMPs) on cardiovascular disease prognosis is still uncertain, the ECM could be a promising therapeutic target in atherothrombotic disease, and several MMP inhibitors are currently undergoing clinical trials (AU)

Atheroembolism during percutaneous renal artery revascularization.

INTRODUCTION: Atheroembolization during renal artery angioplasty and stenting (RA-PTAS) has been postulated as a cause for the inferior renal function results observed when compared with those with surgical revascularization. To further characterize procedure-associated atheroembolism, we analyzed recovered atheroembolic debris and clinical data from patients undergoing RA-PTAS with distal embolic protection (DEP). METHODS: RA-PTAS procedures were performed with DEP using a commercially available temporary balloon occlusion and aspiration catheter system between July 2005 and December 2006. Following RA-PTAS but prior to deflation of the distal occlusion balloon, the static column of blood proximal to the balloon was aspirated and submitted for embolic particle analysis. Angiograms, demographics, and laboratory data were reviewed. Glomerular filtration rate (eGFR) was estimated before RA-PTAS and at 4 to 8 weeks postintervention using the abbreviated Modification of Diet in Renal Disease formula. Associations between clinical factors, captured particle counts, and changes in renal function were examined using univariate techniques and multiple linear regression. RESULTS: Twenty-eight RA-PTAS procedures were performed with DEP. Mean total number of embolic particles counted per procedure was 2033 +/- 1553 for particles 20-60 microm and 265 +/- 132 for particles >60 microm. Significant positive associations with quantity of captured particles 20 to 60 microm were observed for African American race (P = .002), predilation (P = .005), and stent diameter (P < .001); a significant negative association was observed for preoperative aspirin use (P =.016). Quantity of captured particles >60 microm was positively associated with ratio of stent to renal artery diameter (P =.009). Change in eGFR was positively associated with preoperative aspirin use (P = .006) and preoperative eGFR (P < .001), while a negative association was observed for captured particle counts >60 microm (P = .015). CONCLUSION: These results demonstrate the liberation of thousands of atheroembolic particles during RA-PTAS. Clinical, anatomic, and device-related factors may be predictive of procedural embolization, and increasing captured particle counts >60 microm were associated with inferior renal function results. Further investigation is warranted to establish relationships between atheroembolism, end organ functional impairment, and clinical responses.

Cholesterol embolization in renal allografts: a clinicopathologic study of 12 cases.

Cholesterol embolization (CE) in renal allografts is a rare occurrence, the natural history and prognostic significance of which is poorly characterized. We studied the clinicopathologic features and outcome of the largest known series of CE in renal allografts and combined our cases with those in the literature. We identified renal allograft biopsies with CE from 1997 to September 2004 at University of Pittsburgh Medical Center (UPMC). All pathology material related to such biopsies were examined and correlated with clinical information to determine the most probable CE source. Among 5435 RAB, 19 from 12 cadaveric transplant recipients comprising 7 males and 5 females (median age=63 y) had CE. Donors consisted of 9 males and 2 females (median age=47 y). One donor's age and sex was unknown. The most probable CE source was recipient in 9 cases and donor in 3 cases. Five had acute renal failure without acute cellular rejection and 2 had CE-specific failed allografts. Of 19 RAB, the most frequent coexisting diagnosis was chronic allograft nephropathy (63%). The median follow-up time was 661 days. Combining UPMC and non-UPMC cases (n=37) revealed a statistically significant loss of grafts with donor-derived (P value=0.00459) and early CE (P value=0.00938). In renal allografts, CE most often correlated with recipient and donor atherosclerosis. It may present with acute renal failure, but usually not acute graft loss. Graft failure is significantly associated with donor-derived and early CE. Although its prognosis may be poor in the setting of primary nonfunction, prolonged graft survival may be seen.

La LDL agregada induce la expresión y la activación de factor tisular en células vasculares mediante un mecanismo inhibible por pravastatina / Aggregated low-density lipoprotein induces tissue factor expression and activity in vascular cells through a mechanism susceptible to pravastatin-mediated inhibition

Introducción. La captación de lipoproteína de baja densidad (LDL) modificada por agregación (LDLag) induce la expresión y la activación del factor tisular (FT) en células musculares lisas de la pared vascular (CMLV). Nuestro objetivo fue investigar el mecanismo involucrado en la inducción de FT por LDLag y la regulación de dicho mecanismo por la pravastatina. Métodos. Las CMLV se preincubaron durante 4 h con pravastatina (0,5 mM), sin y con mevalonato (0,1 mM), geranilgeranil pirofosfato (GGPP) (10 mM) o farnesil pirofosfato (FPP) (10 mM). Posteriormente, las CMLV se incubaron con LDL nativa (LDLn) o LDLag (100 mg/ml) durante 18 h. La expresión de FT se analizó mediante PCR a tiempo real. La actividad procoagulante de FT (APC) se evaluó mediante el ensayo de generación de factor X activado (Xa). La translocación de Rho A se estudió mediante la detección de Rho A en el citoplasma y la membrana. El efecto de la inhibición de Rho A se analizó en CMLV incubadas con la exoenzima C3 (inhibidor específico de Rho A) (25 mg/ml, 24 h). Resultados. Las LDLag indujeron la expresión y la activación de FT concomitantemente al aumento del valor de Rho A en la membrana (23). La pravastatina (0,5 mM) inhibió la expresión de ARNm y la actividad de FT inducida por LDLag en el 52,33 ± 5,17% y en el 28 ± 2%, respectivamente. Este efecto se revirtió por GGPP pero no por FPP, lo que sugiere la implicación de una proteína geranilgeranilada. La exoenzima C3, un inhibidor específico de Rho A, inhibió la expresión de ARNm y la activación de FT inducida por LDLag en el 42 ± 3,3% y en el 41 ± 2,5%, respectivamente. Conclusión. La LDLag aumenta el FT en CMLV mediante un incremento en los valores de Rho A en la membrana y la pravastatina previene este efecto impidiendo la translocación de Rho A. Nuestros resultados contribuyen a explicar el papel crucial de Rho A en la patogénesis de la aterotrombosis y el potencial de las estatinas para prevenir la aterotrombosis (AU)

Introduction. Aggregated low-density lipoprotein (agLDL) strongly induces tissue factor (TF) expression and activation in human vascular smooth muscle cells (VSMC). The aim of this study was to investigate the mechanism involved in agLDL-TF overexpression and agLDL-TF activation, as well as regulation of this mechanism by pravastatin. Methods. VSMC were preincubated with pravastatin (0.5 mM) with or without mevalonate (0.1 mM), geranylgeranyl pyrophosphate (GGPP) (10 mM) and farnesyl pyrophosphate (FPP) (10 mM). The cells were then exposed to native LDL (nLDL) or agLDL (100 mg/ml) for 18 h. TF expression was measured by real-time PCR. TF activity was analyzed by the factor Xa generation test. Rho A traslocation was determined by detection of Rho A antigen in cytoplasmic and membrane fractions. The effect of Rho A inhibition on TF expression and activity was analyzed by preincubation of VSMC with exoenzyme C3 (25 mg/ml, 24 hours). Results. AgLDL significantly increased TF expression and activity concomitantly with an increase in Rho A membrane levels (by 2-fold). Pravastatin (0.5 mM) inhibited agLDL-TF mRNA overexpression and agLDL-TF activation by 52.33 ± 5.17% and 28 ± 2%, respectively. These effects were reverted by GGPP but not by FPP, suggesting involvement of a geranylgeranyl protein. Exoenzyme C3 (a specific Rho A inhibitor) prevented agLDL-TF overexpression and activation by 42 ± 3.3% and 41 ± 2.5%, respectively. Conclusion. AgLDL internalization increases TF expression and activation through Rho A activation while pravastatin prevents this effect by impairing Rho A traslocation. Our results help to explain the major role of Rho A activation in the pathogenesis of atherothrombosis and the potential of statins in atherothrombosis prevention (AU)

Cholesterol crystal embolism--new aspects of an "old" disease.

Cholesterol crystal embolism is increasing in frequency due, on the one hand to the aging of population and, on the other hand, to the great extent of invasive cardiovascular procedures, anticoagulant and thrombolytic therapy. Very often it has a protean symptomatology being considered as a "great masquerader". Due to its particular clinical picture it is sometimes misdiagnosed. This article presents the major clinical manifestations, the diagnostic strategy, the methods of prevention and treatment of this disease.